It has been suggested that natural killer cells may be of prime importance in the immune surveillance mechanism against mutating cells and tumor rejection. The unique immunologically "virgin" germfree, colostrum-deprived piglets obtained by aseptic hysterectomy from specific pathogen-free Minnesota miniature swine model will be used to investigate and define the cellular nature of natural killer (NK) cells in spontaneous cell-mediated cytotoxicity (SCC) and killer (K) cells in antibody-dependent cell-mediated cytotoxicity (ADCC); and ontogenic development of NK cells in SCC and K cells in ADCC. A four-hour 51Cr-release assay method will be used for cytolytic effector activity for both NK cells in SCC and K cells in ADCC. The human myeloid tumor cell line K563 and/or human T cell line HSB are suitable targets for NK cells in SCC-assay and TNP-conjugated human B cell line SB (TNP-SB) coated with IgG porcineanti-TNP anf/or chicken erythrocytes (CE) coated with IgG rabbit anti-CE are suitable targets for K cells in ADCC-assay. Allogeneic targets with porcine lymphoid cell line P3064-4 and isogeneic targets from autologous thymocytes stimulated with PHA for two days will also be used for NK cells in SCC-assay. In addition, various factors inducing or activating NK and K cells as well as inhibiting or suppressing factors will also be investigated to study regulation of NK and K cell activities.